Acalculous Cholecystitis caused by Histoplasma capsulatum in a severely immunosuppressed HIV-infected patient.

Abstract

Billiary tract involvement in the course of disseminated histoplasmosis has been rarely reported. Here we present a severely immunosuppressed HIV-infected patient who presented with symptomatic acalculous cholecystitis caused by Histoplasma capsulatum.

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Case Report

Acalculous Cholecystitis caused by Histoplasma capsulatum in a severely
immunosuppressed HIV-infected patient

Jorge Alave1, Beatriz Bustamante1,3, Leslie Soto2,3, Jaime Cáceres4, Carlos Seas1,3

1Departamento de Enfermedades Infecciosas, Tropicales y Dermatológicas, Hospital Nacional Cayetano Heredia,
Lima, Peru
2Departamento de Medicina Interna, Hospital Nacional Cayetano Heredia, Lima, Peru
3Instituto de Medicina Tropical Alexander von Humboldt. Universidad Peruana Cayetano Heredia, Lima, Peru
4Departamento de Patología, Hospital Nacional Cayetano Heredia, Lima, Peru

Abstract
Billiary tract involvement in the course of disseminated histoplasmosis has been rarely reported. Here we present a severely
immunosuppressed HIV-infected patient who presented with symptomatic acalculous cholecystitis caused by Histoplasma capsulatum.

Key words: histoplasmosis; HIV; billiary tract

J Infect Dev Ctries 2011; 5(3):235-238.

(Received 01 September 2010 – Accepted 12 November 2010)

Copyright © 2011 Alave et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction
Biliary tract involvement is a well-recognized
complication of advanced HIV infection [1,2]. HIV-
associated cholangiopathy and acalculous
cholecystitis are the most common clinical
manifestations of biliary affection in these patients,
and cytomegalovirus and Cryptosporidium sp. are the
most common causative agents [3]. Infections with
Histoplasma capsulatum are also well-known
complications of advanced HIV infection, presenting
with widespread involvement and overwhelming
severity [4]. Biliary tract involvement by H.
capsulatum has been rarely reported in both HIV and
non-HIV infected patients [5]. We report a case of
acalculous cholecystitis in the course of disseminated
histoplasmosis in a severely immunosuppressed HIV-
infected patient.

Case report
A 23-year-old HIV-infected male patient was
transferred to our hospital for evaluation of persistent
fever, despite receiving standard treatment for
suspected smear negative pulmonary tuberculosis for
one month. The patient presented to the referring
hospital with a three-week history of fever, cough
and weight loss. Laboratory evaluations at that time
included several negative sputum smears for acid-fast
bacilli and fungi, and positive ELISA and Western
blot tests for HIV infection. The CD4 cell count was
33 cells/l, and the viral load 268,000 copies/ml.
The patient was born in the rainforest of Peru, but
was living in Lima for the last eight years, and denied
history of recent travel. The physical examination on
admission to our hospital revealed a febrile patient in
no acute distress; several macular violaceous lesions
were noticed on the face, chest and upper extremities.
No lymphadenopathy or visceromegaly was detected.
Diffuse and bilateral pulmonary rales were heard on
auscultation. Laboratory examinations revealed mild
normocytic-normochromic anemia (hemoglobin of
10g/dl); leukopenia (total WBC of 3140 cells/mm3
with 86% neutrophils and 10% lymphocytes); mild
thrombocytopenia (168,000 cells/mm3); very high
LDH serum values (20,000 IU/dl); and mildly
elevated liver enzymes (ALT was 1.5 times above
normal limit). The chest X ray revealed a diffuse
interstitial infiltrate involving predominantly the
lower lung fields. Repeated Ziehl-Neelsen stains of
sputum samples were negative. Giemsa stains of a
sputum sample and of a bone marrow aspiration were
positive for intracellular yeasts compatible with H.
capsulatum. A serologic immunodiffusion test was

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J Infect Dev Ctries 2011; 5(3):235-238.
236
positive for band M of H. capsulatum, and bone
marrow culture yielded H. capsulatum. The patient
was started on intravenous
deoxycholate at the dose of 1mg/kg/d. Two days after
initiating treatment the patient complained of severe
right upper quadrant pain, nausea and vomiting.
Marked abdominal guarding and positive Murphy
sign were found on physical examination. An
abdominal ultrasound revealed thickening of the
gallbladder wall surrounded by edema, but no
gallstones or dilatation of bile ducts were observed. A
laparoscopic cholecystectomy
Histopathological evaluation of the gallbladder
showed an inflammatory reaction mainly composed
by histiocytes with intracellular yeasts consistent
with H. capsulatum (Figure 1). The patient received
two weeks of amphotericin B deoxycholate (total
cumulative dose of 720 mg) followed by oral
itraconazole. Combination antiretroviral therapy with
stavudine, lamivudine,
atazanavir was started four weeks after. The clinical
evolution was favorable; the last evaluation of the
patient when he was receiving six months of
treatment disclosed a CD4 cell count of 59 cells/l
and a viral load of 198 copies/ml.

amphotericin B
was performed.
and ritonavir boosted
Discussion
Histoplasmosis is a deep mycosis with worldwide
distribution. Clinical manifestations of histoplasmosis
are diverse, ranging from acute self-limited
pulmonary involvement occurring in travelers
exposed to aerosol acquired
disseminated disease, which results from reactivation
of latent foci and is mainly observed in
immunodeficient hosts
disseminated histoplasmosis (PDH) is a severe
presentation of histoplasmosis
predominantly in immunosuppressed patients [8].
The estimated lifetime incidence rates of PDH in
HIV-infected patients living in endemic areas is 5-
20% [9]; 95% of these infections occur in patients
with CD4 cell counts below 150 cells/l [10]. PDH
may follow an acute and usually fulminant clinical
course or a more protracted and indolent course over
several months [6]. The reticuloendothelial system is
preferentially affected
generalized lymphadenopathy and visceromegaly, but
widespread involvement of the kidneys, heart, skin
and the CNS has been
Gastrointestinal involvement has been recognized in
70-90% in necropsy studies of patients with PDH
[11]. Affection of the terminal ileum and of the
infection, to
[6,7]. Progressive
occurring
and manifested with
documented [4].
Figure 1. Histopathological section of the gallbladder stained with PAS.
Gallbladder section showing inflammatory reaction in the subserosal layer and multiple small intracellular yeast forms of approximately 2m (PAS stain, 1000x).

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lymphatic tissue surrounding the small intestine was
the hallmark of gastrointestinal histoplasmosis in
these reports. Interestingly,
manifestations of disease were rare in these patients,
being reported in only 3-12% [5]. Reasons for the
dissociation between clinical manifestations and
pathological involvement are likely due to very subtle
and non-specific clinical
underdiagnosis.
Biliary tract involvement in the course of
histoplasmosis and PDH has been rarely reported.
Two previous reports documented extra-hepatic
biliary tract obstruction in two non HIV-infected
pediatric patients who presented with abdominal pain
as the main clinical manifestation [12,13]. One of
these cases was a
lymphoblastic leukemia [12], and the other one was a
ten-year-old girl with
immunosuppressive conditions [13]. The largest case
series published to date of biliary tract involvement
in HIV-infected patients did not document any case
of PDH among 107 AIDS patients who underwent
cholecystectomy [14]. Two subsequent reports
documented biliary tract involvement in the course of
PDH in HIV-infected patients [15,16]. In one of these
reports, a 20-year-old
immunosuppressed patient, with a past history of
PDH, non-compliant to anti-retroviral therapy (last
CD4 cell count was 3 cells/l) presented for
evaluation of epigastric pain, nausea, vomiting and
fever of five days duration. A duodenal ulcer with
associated dilatation of the common bile duct
presumably due to extrinsic compression of either
adjacent lymph nodes or from a fluid collection
within the neighboring
documented [15]. The second report described
thickening of the duodenum with an erythematous
and friable duodenal mucosa, dilatation of intra and
extra-hepatic bile ducts, and distal stenosis of the
common bile duct, which were observed in a 34-year-
old male patient who presented with abdominal pain
and weight loss two months after starting
antiretroviral therapy [16]. A CD4 count of 12
cells/l and a viral load < 48 copies/ml were
documented on admission. The clinical presentation
after initiation of antiretroviral treatment suggested
immune reconstitution inflammatory syndrome of
unmasking histoplasmosis in this case. Our patient
clinically differed from these two previously reported
HIV-infected cases. He developed the sub-acute and
progressive form of PDH with evidence of
pulmonary and bone marrow involvement, and
clinical evident
manifestations or
six-year-old boy with
no recognized
female severely
intestinal wall was
presented
acalculous cholecystitis with no evidence of bile duct
involvement. Abdominal ultrasound was a helpful
diagnostic tool in our patient and a laparoscopic
cholecystectomy was indicated for his treatment.
Further histopathological studies confirmed the
gallbladder invasion by H. capsulatum. Intestinal
involvement in this case could not be ruled out as
intestinal endoscopies were not performed.
To our knowledge, this is the first report of PDH
presenting with symptomatic acalculous cholecystitis
in HIV-infected patients. Gallbladder involvement
should be incorporated in the list of gastrointestinal
organs affected in the course of PDH.

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Corresponding author
Carlos Seas, MD
Universidad Peruana Cayetano Heredia
Av. Honorio Delgado 430, Lima 31, Peru
Telephone: 51-1-4823910
Fax: 51-1-4823404
Email: cseas2@gmail.com

Conflict of interests: No conflict of interests is declared.